Tr. Hanley et al., Developmental toxicity studies in rats and rabbits with 3,5,6-trichloro-2-pyridinol, the major metabolite of chlorpyrifos, TOXICOL SCI, 53(1), 2000, pp. 100-108
3,5,6-Trichloro-2-pyridinol (TCP), the primary metabolite of chlorpyrifos a
nd chlorpyrifos-methyl, was evaluated for potential developmental toxicity.
Groups of 32-34 bred female Fischer 344 rats were given 0, 50, 100, or 150
mg TCP/kg/day by gavage on gestation days 6-15; the fetuses were evaluated
on gestation day 21. Similarly, groups of 16 inseminated female New Zealan
d White rabbits were given 0, 25, 100, or 250 mg TCP/kg/day by gavage on ge
station days 7-19, and fetuses were evaluated on gestation day 28. No clini
cal signs of toxicity attributed to TCP were noted in either species. In ra
ts, at 150 mg/kg/day, maternal effects included slight decreases in feed co
nsumption, significantly depressed body weight gain (25% relative to contro
ls) resulting in significantly lower maternal terminal body weights, and in
creased relative liver weight. At 100 mg/kg/day, maternal body weight gain
in rats was depressed approximately 22%. Among rabbits, maternal effects we
re limited to the group given 250 mg/kg/day, which lost an average of appro
ximately 70 g during the treatment period (vs. 140 g in the controls). Ther
e were no effects on fetal weight or viability, nor were there significant
increases in any fetal alteration in either species. A slightly higher (not
statistically significant) than usual incidence of central nervous system
anomalies occurred in rabbits, but these anomalies were found in both treat
ed and control groups in this study as well as contemporaneous studies of u
nrelated compounds. This, and the fact that these anomalies were not seen w
ith the parent compound, chlorpyrifos, suggest that their origin was sponta
neous. Thus, TCP was not considered fetotoxic or teratogenic in either rats
or rabbits, even at dose levels that produced maternal toxicity.